Polyurethanes represent a main class of synthetic elastomers employed for long-term, medical implants as they present tunable chemical properties, excellent mechanical properties, good blood compatibility, and also can be designed to degrade in biological environments [A. Rechichi et al., J. Biomed. Mater. Res., 84-A, 847 (2008)]. More specifically, polyether-urethane (PEU) and polyether-urethane-urea (PEUU) elastomers have long been considered ideal for use in many implanted devices, in spite of occasionally cited drawbacks [M. A. Schubert et al., J. Biomed. Mater. Res., 35, 319 (1997); B. Ward et al., J. Biomed. Mater. Res., 77-A, 380 (2008)]. Of the cited drawbacks are those associated with (1) the generation of aromatic diamines, which are considered to be toxic upon degradation of segmented copolymers made using aromatic diisocyanates for interlinking; (2) chain degradation due to oxidation or radiation degradation of the polyether component of segmented copolymers, and particularly those which encounter frequent mechanical stresses in the biological environment; and (3) chemical degradation in chemically and mechanically hostile biological environments of the urethane links of segmented copolymers and particularly those comprising reactive aromatic urethane linkages.
Liquid solventless, complex polymeric compositions, which thermoset at ambient temperatures through additional polymerization of a two-component system, wherein the first component comprises amine or acrylate-terminated polyurethanes or polyurethane-ureas and the second component comprises di- or polyacrylates have been described in U.S. Pat. No. 4,742,147. However, the prior art is virtually silent on self-standing PEU and PEUU liquid solventless compositions for use in pharmaceutical formulations and/or medical devices. Similarly, the prior art on polyether-urethanes is practically silent on hydroswellable (or water-swellable) systems, in spite of the fact that it addresses elastomeric, segmented, hydrophilic polyether-urethane-based, lubricious coating compositions based on aromatic diisocyanate and polyethylene glycol (U.S. Pat. No. 4,990,357)—it did not suggest a self-standing material for medical device applications. This prompted a study subject of a recent disclosure by one inventor of the instant invention and his coworkers (U.S. patent application Ser. No. 12/380,391). The latter disclosure dealt in general with hydroswellable, absorbable and non-absorbable, aliphatic, segmented polyurethanes and polyurethane-urea capable of swelling in the biological environment with associated increase in volume of at least 3 percent have more than one type of segments, including those derived from polyethylene glycol and the molecular chains are structurally tailored to allow the use of corresponding formulations and medical devices as carriers for bioactive agents, rheological modifiers of cyanoacrylate-based tissue adhesives, as protective devices for repairing defective or diseased components of articulating joints and their cartilage, and scaffolds for cartilage tissue engineering.
Most pertinent to the instant invention are certain composition and formulations described in U.S. patent application Ser. No. 12/380,391, which can be used as (1) injectable gel-forming liquid formulations for the controlled delivery of bioactive agents for treating periodontitis, nail infections, bone infections, a variety of bacterial and fungal infections, and different forms of cancers, and (2) in situ-forming, extrudable luminal liner for the controlled drug delivery at the luminal wall of vaginal canals and blood vessels. However, the use of these compositions as covers or liners on the luminal wall of vaginal canals, esophagi, and blood vessels may be less than optimum since the teaching of U.S. patent application Ser. No. 12/380,391 deals mostly with hydroswellable amorphous coatings, which may undergo excessive deformation and creep in presence of low levels of shear stresses. This prompted the study, subject of the present invention, which relates to a new class of absorbable crystalline polyether-ester-urethane-based compositions, which represent a substantial improvement over their amorphous analogs of the prior art, in terms of providing a set of balanced properties that support hydroformation into tissue-adhering liners that are not only resilient, but also resist deformation in the presence of shear forces.